Back to resultsA Study Of The Safety And Efficacy Of PF-04191834 In Patients With Osteoarthritis Of The Knee
Primary Purpose
Osteoarthritis, Knee
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-04191834
PF-04191834 placebo
Naproxen placebo
PF-04191834 placebo
PF-04191834
Naproxen placebo
PF-04191834
Naproxen
PF-04191834 placebo
Naproxen
PF-04191834 placebo
PF-04191834
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis, Knee focused on measuring Cross-over, safety, efficacy, tolerability, osteoarthritis, knee, pain
Eligibility Criteria
Inclusion Criteria:
- Subjects must have a diagnosis of osteoarthritis based on the American College of Rheumatology criteria confirmed by an X-ray
- Subjects must be willing and able to stop all current pain therapy for the duration of the study
- Subjects must be willing and able to complete a daily diary
Exclusion Criteria:
- BMI of >39 kg/m2
- Known allergy or hypersensitivity to naproxen
- Any condition or medical history that might interfere with the subject's ability to complete the study visits and assessments
Sites / Locations
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
PF-04191834 followed by placebo
Placebo followed by PF-04191834
PF-04191834+Naproxen followed by Naproxen
Naproxen followed by PF-04191834+Naproxen
Arm Description
PF-04191834 600 mg BID dose followed by matched placebo plus naproxen placebo.
Placebo followed by 600 mg BID dose of PF-04191834 plus naproxen placebo.
PF-04191834 600 mg BID + Naproxen 500 mg BID followed by Naproxen 500 mg BID plus PF-04191834 placebo
Naproxen 500 mg BID followed by PF-04191834 600 mg BID + Naproxen 500 mg BID
Outcomes
Primary Outcome Measures
Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 1
The WOMAC Pain subscale, comprised of 5 questions regarding the amount of pain experienced in the index joint, was calculated as the mean of the scores from the 5 individual questions. The WOMAC Pain subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-20, with higher scores indicating higher pain.
Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 2
The WOMAC Pain subscale, comprised of 5 questions regarding the amount of pain experienced in the index joint, was calculated as the mean of the scores from the 5 individual questions. The WOMAC Pain subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-20, with higher scores indicating higher pain.
Secondary Outcome Measures
WOMAC Stiffness Domain Score
The WOMAC Stiffness subscale, comprised of 2 questions regarding the amount of stiffness experienced in the index joint, was calculated as the mean of the scores from the 2 individual questions. The WOMAC Stiffness subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-8, with higher scores indicating more stiffness.
WOMAC Physical Function Domain Score
The WOMAC Physical Function subscale refers to the participant's ability to move around and perform usual activities of daily living. The WOMAC Physical Function subscale, comprised of 17 questions regarding the degree of difficulty experienced in the index joint, was calculated as the mean of the scores from the 17 individual questions. The WOMAC Physical Function subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-68, with higher scores indicating worse function.
WOMAC Total Score
The WOMAC total score was calculated as the sum of Pain subscale score (5 questions), Stiffness subscale score (2 questions) and Physical Function subscale score (17 questions), with a total of 24 questions(score range:0=none, 4=extreme) giving a possible total score range from 0 to 96 . lower subscale scores represent less pain, less stiffness, or better physical performance.
Importance Weighted Total WOMAC Score
Importance weighted total WOMAC score was calculated using all subscales including Pain, Stiffness and Physical Function subscales (24 questions in total,score range: 0=none to 4= extreme,giving a possible overall score range of 0-96).Lower subscale scores represent less pain, less stiffness, or better physical performance.
Daily Diary Pain Score During Week 1 of Each Treatment Period
The daily diary pain was assessed using an 11-point numerical rating scale (NRS) ranging from 0 to 10 (0 = no pain; 10 = the worst pain possible).
Daily Diary Pain Score During Week 2 of Each Treatment Period
The daily diary pain was assessed using an 11-point numerical rating scale (NRS) ranging from 0 to 10 (0 = no pain; 10 = the worst pain possible).
Rescue Medication Use
Rescue medication use was collected daily in a daily diary, in which participants noted the amount of rescue medication (number of pills) taken each day. Participants were provided with rescue medication paracetamol/acetaminophen throughout the study including the Washout Period and the Initial Pain Assessment Period. Paracetamol/acetaminophen was taken as needed to a maximum of 2000 mg per day, but must be discontinued 48 hours prior to the Baseline visit (Visit 3). From Visit 3 onwards, participants might take up to 2000 mg of paracetamol/acetaminophen per day up to 3 days per week.
Plasma Concentration of PF-04191834
Urinary Leukotriene E4 (LTE4) Levels
LTE4 is a terminal metabolic product of arachidonic acid by 5-LO. Its synthesis is dependent upon the activity of 5-LO and it is eliminated through urinary clearance. Hence, the level of urinary LTE4 (uLTE4) excretion may be an indicator of endogenous 5-LO activity.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01147458
Brief Title
A Study Of The Safety And Efficacy Of PF-04191834 In Patients With Osteoarthritis Of The Knee
Official Title
A Phase 2 Randomized, Double-Blinded, Double-Dummy, Placebo And Active Controlled Two Cohort Two-Way Cross-Over, Multi-Centre Clinical Trial To Examine The Pain Relief Produced By 2 Weeks Of Daily Oral Administration Of A 5-Lipoxygenase (5-Lox) Inhibitor PF-04191834 Alone And In Combination With Naproxen In Patients With Flare-Enriched Osteoarthritis Of The Knee
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
July 2010 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
PF-04191834 works in animal models by inhibiting one of the enzymes, 5-lipoxygenasein which is involved in the pathway that causes inflammation and pain. The purpose of this study is to test how effective, safe and tolerated PF-04191834 is in patients with osteoarthritis of the knee by itself or with naproxen, particularly to test if patients have less pain.
Detailed Description
This study has been terminated in response to a reported serious adverse event (SAE). The sponsor's assessment of the limited data available at the time of the initial SAE report was that the SAE may alter the potential benefit - risk profile of the study medication.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee
Keywords
Cross-over, safety, efficacy, tolerability, osteoarthritis, knee, pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
190 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-04191834 followed by placebo
Arm Type
Experimental
Arm Description
PF-04191834 600 mg BID dose followed by matched placebo plus naproxen placebo.
Arm Title
Placebo followed by PF-04191834
Arm Type
Experimental
Arm Description
Placebo followed by 600 mg BID dose of PF-04191834 plus naproxen placebo.
Arm Title
PF-04191834+Naproxen followed by Naproxen
Arm Type
Experimental
Arm Description
PF-04191834 600 mg BID + Naproxen 500 mg BID followed by Naproxen 500 mg BID plus PF-04191834 placebo
Arm Title
Naproxen followed by PF-04191834+Naproxen
Arm Type
Experimental
Arm Description
Naproxen 500 mg BID followed by PF-04191834 600 mg BID + Naproxen 500 mg BID
Intervention Type
Drug
Intervention Name(s)
PF-04191834
Intervention Description
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
Intervention Type
Drug
Intervention Name(s)
PF-04191834 placebo
Intervention Description
Matching PF-04191834 placebo tablets to be administered BID for two weeks
Intervention Type
Drug
Intervention Name(s)
Naproxen placebo
Intervention Description
Matching naproxen placebo tablets to be administered BID for 4 weeks
Intervention Type
Drug
Intervention Name(s)
PF-04191834 placebo
Intervention Description
Matching PF-04191834 placebo tablets to be administered BID for two weeks
Intervention Type
Drug
Intervention Name(s)
PF-04191834
Intervention Description
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
Intervention Type
Drug
Intervention Name(s)
Naproxen placebo
Intervention Description
Matching naproxen placebo tablets to be administered BID for 4 weeks
Intervention Type
Drug
Intervention Name(s)
PF-04191834
Intervention Description
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
Intervention Type
Drug
Intervention Name(s)
Naproxen
Intervention Description
Naproxen 500 mg tablet administered BID for a total of four weeks
Intervention Type
Drug
Intervention Name(s)
PF-04191834 placebo
Intervention Description
Matching PF-04191834 placebo tablets to be administered BID for two weeks
Intervention Type
Drug
Intervention Name(s)
Naproxen
Intervention Description
Naproxen 500 mg tablet administered BID for a total of four weeks
Intervention Type
Drug
Intervention Name(s)
PF-04191834 placebo
Intervention Description
Matching PF-04191834 placebo tablets to be administered BID for two weeks
Intervention Type
Drug
Intervention Name(s)
PF-04191834
Intervention Description
100 mg tablets of PF-04191834 to provide a 600 mg BID dose administered for two weeks
Primary Outcome Measure Information:
Title
Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 1
Description
The WOMAC Pain subscale, comprised of 5 questions regarding the amount of pain experienced in the index joint, was calculated as the mean of the scores from the 5 individual questions. The WOMAC Pain subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-20, with higher scores indicating higher pain.
Time Frame
Baseline (Day 1 of Visit 3) and end of treatment Period 1 (Day 15+1 of Visit 5)
Title
Change From Baseline in Western Ontario & McMaster (WOMAC) Osteoarthritis Index Pain Score at the End of Treatment Period 2
Description
The WOMAC Pain subscale, comprised of 5 questions regarding the amount of pain experienced in the index joint, was calculated as the mean of the scores from the 5 individual questions. The WOMAC Pain subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-20, with higher scores indicating higher pain.
Time Frame
Baseline (Day 28 of Visit 7) and end of treatment Period 2 (Day 43+1 of Visit 9)
Secondary Outcome Measure Information:
Title
WOMAC Stiffness Domain Score
Description
The WOMAC Stiffness subscale, comprised of 2 questions regarding the amount of stiffness experienced in the index joint, was calculated as the mean of the scores from the 2 individual questions. The WOMAC Stiffness subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-8, with higher scores indicating more stiffness.
Time Frame
Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2
Title
WOMAC Physical Function Domain Score
Description
The WOMAC Physical Function subscale refers to the participant's ability to move around and perform usual activities of daily living. The WOMAC Physical Function subscale, comprised of 17 questions regarding the degree of difficulty experienced in the index joint, was calculated as the mean of the scores from the 17 individual questions. The WOMAC Physical Function subscale scores for each question range from 0 to 4 giving a possible overall score range of 0-68, with higher scores indicating worse function.
Time Frame
Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2
Title
WOMAC Total Score
Description
The WOMAC total score was calculated as the sum of Pain subscale score (5 questions), Stiffness subscale score (2 questions) and Physical Function subscale score (17 questions), with a total of 24 questions(score range:0=none, 4=extreme) giving a possible total score range from 0 to 96 . lower subscale scores represent less pain, less stiffness, or better physical performance.
Time Frame
Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2
Title
Importance Weighted Total WOMAC Score
Description
Importance weighted total WOMAC score was calculated using all subscales including Pain, Stiffness and Physical Function subscales (24 questions in total,score range: 0=none to 4= extreme,giving a possible overall score range of 0-96).Lower subscale scores represent less pain, less stiffness, or better physical performance.
Time Frame
Baseline (Day 1 of Visit 3 for Period 1 and Day 28 of Visit 7 for Period 2), Day 15+1 of Visit 5 for Period 1, and Day 43+1 of Visit 9 for Period 2
Title
Daily Diary Pain Score During Week 1 of Each Treatment Period
Description
The daily diary pain was assessed using an 11-point numerical rating scale (NRS) ranging from 0 to 10 (0 = no pain; 10 = the worst pain possible).
Time Frame
4 days prior to baseline visits (Visits 3 for Period 1 and Vist 8 for Period 2) up to 7 days after baseline visits
Title
Daily Diary Pain Score During Week 2 of Each Treatment Period
Description
The daily diary pain was assessed using an 11-point numerical rating scale (NRS) ranging from 0 to 10 (0 = no pain; 10 = the worst pain possible).
Time Frame
Over the last 4 days before baseline visits (Visits 3 for Period 1 and Visit 8 for Period 2) and over the last 6 days before Visit 5 for Period 1 and Visit 9 for Period 2
Title
Rescue Medication Use
Description
Rescue medication use was collected daily in a daily diary, in which participants noted the amount of rescue medication (number of pills) taken each day. Participants were provided with rescue medication paracetamol/acetaminophen throughout the study including the Washout Period and the Initial Pain Assessment Period. Paracetamol/acetaminophen was taken as needed to a maximum of 2000 mg per day, but must be discontinued 48 hours prior to the Baseline visit (Visit 3). From Visit 3 onwards, participants might take up to 2000 mg of paracetamol/acetaminophen per day up to 3 days per week.
Time Frame
Day -7 (Visit 2) up to 28-day follow-up (Visit 10)
Title
Plasma Concentration of PF-04191834
Time Frame
Pre-dose and post-dose (1 to 3 hours) on Days 1, 8, 15, 29, 36, and 43
Title
Urinary Leukotriene E4 (LTE4) Levels
Description
LTE4 is a terminal metabolic product of arachidonic acid by 5-LO. Its synthesis is dependent upon the activity of 5-LO and it is eliminated through urinary clearance. Hence, the level of urinary LTE4 (uLTE4) excretion may be an indicator of endogenous 5-LO activity.
Time Frame
Day -7 (Visit 2) up to Day 43 (Visit 9 or End of Treatment Period 2)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must have a diagnosis of osteoarthritis based on the American College of Rheumatology criteria confirmed by an X-ray
Subjects must be willing and able to stop all current pain therapy for the duration of the study
Subjects must be willing and able to complete a daily diary
Exclusion Criteria:
BMI of >39 kg/m2
Known allergy or hypersensitivity to naproxen
Any condition or medical history that might interfere with the subject's ability to complete the study visits and assessments
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Peoria
State/Province
Arizona
ZIP/Postal Code
85381
Country
United States
Facility Name
Pfizer Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Pfizer Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85015
Country
United States
Facility Name
Pfizer Investigational Site
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Pfizer Investigational Site
City
Carmichael
State/Province
California
ZIP/Postal Code
95608
Country
United States
Facility Name
Pfizer Investigational Site
City
Fair Oaks
State/Province
California
ZIP/Postal Code
95628
Country
United States
Facility Name
Pfizer Investigational Site
City
San Diego
State/Province
California
ZIP/Postal Code
92128
Country
United States
Facility Name
Pfizer Investigational Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80209
Country
United States
Facility Name
Pfizer Investigational Site
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Pfizer Investigational Site
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
Pfizer Investigational Site
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Pfizer Investigational Site
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Pfizer Investigational Site
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States
Facility Name
Pfizer Investigational Site
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
Facility Name
Pfizer Investigational Site
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01610
Country
United States
Facility Name
Pfizer Investigational Site
City
Edina
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Facility Name
Pfizer Investigational Site
City
St. Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
Facility Name
Pfizer Investigational Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89144
Country
United States
Facility Name
Pfizer Investigational Site
City
Monroe
State/Province
North Carolina
ZIP/Postal Code
28112
Country
United States
Facility Name
Pfizer Investigational Site
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58103
Country
United States
Facility Name
Pfizer Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43213
Country
United States
Facility Name
Pfizer Investigational Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Pfizer Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19139
Country
United States
Facility Name
Pfizer Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Pfizer Investigational Site
City
Arlington
State/Province
Virginia
ZIP/Postal Code
22205
Country
United States
Facility Name
Pfizer Investigational Site
City
St. John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1A 3R5
Country
Canada
Facility Name
Pfizer Investigational Site
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 1Z1
Country
Canada
Facility Name
Pfizer Investigational Site
City
Quebec
ZIP/Postal Code
G1V 3M7
Country
Canada
Facility Name
Pfizer Investigational Site
City
Quebec
ZIP/Postal Code
G1W 4R4
Country
Canada
Facility Name
Pfizer Investigational Site
City
Goteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Pfizer Investigational Site
City
Stockholm
ZIP/Postal Code
115 22
Country
Sweden
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B0041007&StudyName=A%20Study%20Of%20The%20Safety%20And%20Efficacy%20Of%20PF-04191834%20In%20Patients%20With%20Osteoarthritis%20Of%20The%20Knee
Description
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Learn more about this trial
A Study Of The Safety And Efficacy Of PF-04191834 In Patients With Osteoarthritis Of The Knee
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